This project is an attempt to find a fundamental theory of how macromolecules operate. The study began by asking how molecules such as repressors, polymerases and ribosomes are able to locate specific patterns (binding sites) on DNA or RNA. The methods of information theory so successfully used by electrical engineers and computer scientists were applied to this problem. Using these toots, we can show quantitatively that the amount of pattern in the binding sites is just sufficient for the sites to be located in the genome (Schneider 1986, Schneider 1988, Schneider 1989). To explain these results, a general theory is being developed that quantitatively explains the precision macromolecules exhibit while performing their tasks. The theory ties Shannon's communications theory to molecular biology. The techniques being formulated in this project include pattern searching techniques that are more precise than the well known "consensus sequence", and a general cloning technique that can be used to quantitatively define the patterns of a binding site or other functional region of nucleic-acid sequence. The project involves three lines of work: (1) analysis of known DNA or RNA binding site patterns to test the hypothesis that the pattern at binding sites is related to their number in the genome; (2) bench work to dissect those binding sites which provide critical tests of the theory; and (3) extension of the theory to describe all specific molecular interactions.